IBUPROFEN/PARACETAMOL

Posology For short term-use only. The patient should consult a doctor if the symptoms persist or worsen or if the medicinal product is required for more than 3 days. 4).

Adults:

One tablet to be taken up to three times per day with water. The interval between single doses should be at least six hours. If single doses of one tablet do not control symptoms, a maximum of two tablets may be taken up to three times a day.

The interval between single doses should be at least six hours. The maximum dose is six tablets (1200 mg ibuprofen, 3000 mg paracetamol) in any 24 hours period. 4). The elderly are at increased risk of the serious consequences of adverse reactions.

If an NSAID is considered necessary, the lowest effective dose should be used for the shortest possible duration. The patient should be monitored regularly for gastrointestinal bleeding during NSAID therapy. Paediatric population Not for use by children and adolescents under 18 years.

Method of administration Oral use. To minimise side effects, patients should take Ibuprofen/Paracetamol with food.

Clinical trials with ibuprofen/paracetamol have not indicated any other undesirable effects other than those for ibuprofen or paracetamol alone. Tabulated list of adverse reactions The following table lists adverse effects from pharmacovigilance data experienced by patients taking ibuprofen alone or paracetamol alone in short-term and long- term use, tabulated by system organ class and frequency.

Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.

System Organ Class Frequency Adverse Event Blood and lymphatic system disorders Very rare Haematopoietic disorders (agranulocytosis, anaemia, aplastic anaemia, haemolytic anaemia leucopenia, neutropenia, pancytopenia and thrombocytopenia).

First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising and nose bleeding. Immune system disorders Very rare Hypersensitivity reactions1 have been reported.

These may consist of non-specific allergic reactions and anaphylaxis. Severe hypersensitivity reactions. Symptoms can include: facial, tongue and larynx swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock).

Psychiatric disorders Very rare Confusion, depression and hallucinations Uncommon Headache and dizzinessNervous system disorders Very rare Paraesthesia, optic neuritis and somnolence. 4). Eye disorders Very rare Visual disturbance Ear and labyrinth disorders Very rare Tinnitus and vertigo Cardiac disorders Very rare Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.

4). Not known Kounis syndrome Respiratory, thoracic and mediastinal disorders Very rare Respiratory reactivity including: asthma, exacerbation of asthma, bronchospasm and dyspnoea. 4). 4). Less frequently gastritis has been observed and pancreatitis reported.

Hepatobiliary disorders Very rare Abnormal liver function, hepatitis and jaundice. 9). Uncommon Rashes of various types including pruritis and urticaria. Angioedema and swelling face. Very rare Severe cutaneous adverse reactions (SCARs) ( including Erythema multiforme, exfoliative dermatitis, Stevens JohnsonSyndrome and Toxic Epidermal Necrolysis.

Skin and subcutaneous tissue disorders Not known Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), Acute generalised exanthematous pustulosis (AGEP) Metabolism and Nutrition Disorders Not known Decreased Appetite Not known Hypokalaemia2 Not known High anion gap metabolic acidosis3 Very rare Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and acute and chronic renal failure.

Not known Ureteric colic, dysuria Renal and urinary disorders Not known Renal tubular acidosis2 General disorders and administration site conditions Very rare Fatigue and malaise. Common Alanine aminotransferase increased, gamma-glutamyltransferase increased and liver function tests abnormal with paracetamol.

Blood creatinine increased, blood urea increased Investigations Uncommon Aspartate aminotransferase increased, blood alkaline phosphatase increased, blood creatine phosphokinease increased, haemoglobin decreased and platelet count increased.

Description of selected adverse reactions 1Hypersensitivity reactions have been reported. g. g. pruritus, urticaria, angioedema and, more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis, and erythema multiforme).

2Renal tubular acidosis and hypokalaemia have been reported in the post- marketing setting typically following prolonged use of the ibuprofen component at higher than recommended doses. 4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended.

The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors. The hazard of paracetamol overdose is greater in patients with non-cirrhotic alcoholic liver disease.

Immediate medical advice should be sought in the event of an overdose, even if the patient feels well, because of the risk of delayed, serious liver damage. 2). 2).

Caution is required in patients with certain conditions: • Respiratory disorders:

In patients suffering from, or with a history of, bronchial asthma or allergic disease, NSAIDs have been reported to precipitate bronchospasm. • Cardiovascular, renal and hepatic impairment: The administration of NSAIDs may cause a dose dependent reduction in prostaglandin formation and precipitate renal impairment.

Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. 3). Renal tubular acidosis and hypokalaemia may occur following acute overdose and in patients taking ibuprofen products over long periods at high doses (typically greater than 4 weeks), including doses exceeding the recommended daily dose.

• Cardiovascular and cerebrovascular effects: Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

g. myocardial infarction or stroke). g. ≤1200 mg/day) is associated with an increased risk of arterial thrombotic events. Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg/day) should be avoided.

g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) particularly if high doses of ibuprofen (2400 mg/day) are required. Cases of Kounis syndrome have been reported in patients treated with Ibuprofen/Paracetamol 200/500 mg film-coated tablets.

Kounis syndrome has been defined as cardiovascular symptoms secondary to an allergic or hypersensitive reaction associated with constriction of coronary arteries and potentially leading to myocardial infarction. • Gastrointestinal bleeding, ulceration and perforation: Gastrointestinal (GI) bleeding, ulceration and perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

3) and in the elderly. These patients should commence treatment on the lowest dose available. g. 5). Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

5). When GI bleeding or ulceration occurs in patients receiving ibuprofen-containing medicinal products, the treatment should be withdrawn. 8). 8). • Severe cutaneous adverse reactions (SCARs): Severe cutaneous adverse reactions (SCARs),, including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome), and acute generalized exanthematous […]

1. g. bronchospasm, angioedema, asthma, rhinitis, or urticaria) associated with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs). - In patients with active, or a history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

4). - Patients with defects in coagulation. 4). 5). 5). 6) SUMMARY OF PRODUCT CHARACTERISTICS 4 CLINICAL PARTICULARS